Comparing Between CO2 and Phenylephrine Treatment in Patients With Progressive Lacunar Infarction (CARBOGEN Study)

Comparing Between CO2 and Phenylephrine Treatment in Patients With Progressive Lacunar Infarction (CARBOGEN Study)

Comparing Between CO2 and Phenylephrine Treatment in Patients With Progressive Lacunar Infarction (CARBOGEN Study)

Lacunar infarction is an ischemic stroke occurred by small perforating artery occlusion . Twenty percent of ischemic stroke is lacunar infarction. However, outcome of lacunar infarction is excellent, about 20-40% patients are suffered neurological worsening. Progressive lacunar infarction is associated poor functional outcome and neurological deficit. Currently, no treatment for progressive lacunar infarction is recommended on the guideline. Several small study reported that phenylephrine and magnesium may be helpful for progressive lacunar infarction. Carbogen is a mixture of 5% CO2 with 95% O2. Carbogen is safe and it is used for the treatment of sudden sensory neural hearing loss or ocular ischemia. CO2 dilate cerebral arteriole and concentration of CO2 is correlated with cerebral blood flow. Lacunar infarction is small and perfused with marginal flow by neighboring perforating arteriole. Increased cerebral blood flow following dilation of cerebral arteriole by CO2 might halt and revert progressive lacunar infarction. Induced hypertension is alternative treatment of progressive lacunar infarction. Increasing blood pressure also induce cerebral blood flow. Phenylephrine is an α1 agonist, phenylephrine act on peripheral artery and little effect on cerebral artery or heart. Several studies reported that the effectiveness of phenylephrine on progressing stroke. Therefore, this study will compare the effectiveness of carbogen versus phenylephrine in lacunar infarction patients who suffered neurological worsening.

The study is a single center, prospective, randomized, open-label trial with blinded end-point assessment (PROBE) design study. For the patients with neurological worsening after lacunar infarction, the carbogen group and the phenylephrine group will be randomized by 1: 1. Patients will be enrolled from April 2021 to December 2022 (based on the date of stroke). We will collect medical history, laboratory findings, neurological scores, and functional recovery. Functional recovery scores are performed by independent researchers in the blind state. All data is collected using e-CRF, and the image study will be anonymized and sent to the central adjudication. Central adjudication will review the image study.

Three months after discharge, the independence assessment will be performed by the researcher who don't know the patients group.

Side effect (cerebral hemorrhage, myocardial infarction, Losing consciousness, difficulty breathing, dizziness, fatigue, headache, anxiety, etc)

Inclusion Criteria: Age ≥20 years Anterior circulation progressive lacunar infarction. Neurological worsening either 1 point in NIHSS score or MRC grade Exclusion Criteria: Age <20 Cortical infarction Posterior circulation lacunar infarction Relevant artery stenosis more than 50% or occlusion Moyamoya disease Difficulty in inhalation of Carbogen (panic, severe anxiety disorder) Drug allergy for phenylephrine Persistent bradycardia (pulse rate < 50 /min) History of hemorrhagic stroke Pre-stroke mRS ≥2